Low-density lipoprotein (LDL) receptors (LDLRs) are cell surface receptors involved in general intracellular membrane cycling and endocytosis. The functions of LDLRs include (1) cargo transport for internalizing extracellular components into the endosomal compartment, and (2) lipoproteins metabolism for maintaining cholesterol homeostasis in the body.
LDLRs are members of a receptor superfamily, which also includes LDL receptor-related proteins (LRPs). The roles of LRPs are more restricted than that of LDLRs in lipid metabolism. However, in addition to cargo transport and lipid metabolism, the LRPs are also involved in other cellular processes such as signal transduction that significantly impacts cell metabolism and physiology.
Several LRPs have been identified, including LRP-1, LRP-1b, LRP-2, LRP-5, LRP-6, LRP-7, LRP-8, LRP-9, LRP-10, and LRP-11 (Strickland et al. (2002) Trends in Endocrinology and Metabolism 13(2): 66–74; Herz and Strickland (2001) The Journal of Clinical Investigation 108(6): 779–784; and Herz (2001) Neuron 29: 571–581). All LRPs, like LDLRs, contain trans-membrane sequences and are multi-functional proteins. LRPs differ from each other in minor ways, and have similar structural motifs, including, for example, EGF-like repeats, YWTD repeats, O-linked sugar domains, complement-like repeats, and a cytoplasmic domain. LRPs bind to many intracellular and extracellular molecules. Such intracellular molecules include adaptor and scaffold proteins (e.g., Dab-1, FE65, and PSD-95) and such extracellular molecules include lipoproteins, proteinases, bacterial toxins, antibiotics, viruses and proteinase inhibitor complexes.
Lactoferrin, an 80 kDa glycoprotein present in milk and epithelial secretions, is released by inflammatory cells during immune responses. It circulates at a concentration of 2–7 μg/ml in plasma, and is believed to be involved in regulation of iron metabolism, immunity, and embryonic development.